Wednesday, February 27, 2013

A new study finds that for some chronic pain sufferers, avoiding the harmful effects of stress may be key to managing their condition. As such, stress management techniques and relaxation or meditation training is highly recommended for individuals with chronic pain.

In a study that appears in the journal Brain, University of Montreal researchers say stress management is particularly important for people with a smaller-than-average hippocampus, as these individuals seem to be particularly vulnerable to stress.

"Cortisol, a hormone produced by the adrenal glands, is sometimes called the 'stress hormone' as it is activated in reaction to stress. Our study shows that a small hippocampal volume is associated with higher cortisol levels, which lead to increased vulnerability to pain and could increase the risk of developing pain chronicity," said researcher and doctoral student Étienne Vachon-Presseau.

As neuropsychologist Dr. Pierre Rainville said, "Our research sheds more light on the neurobiological mechanisms of this important relationship between stress and pain. Whether the result of an accident, illness or surgery, pain is often associated with high levels of stress.

"Our findings are useful in that they open up avenues for people who suffer from pain to find treatments that may decrease its impact and perhaps even prevent chronicity. To complement their medical treatment, pain sufferers can also work on their stress management and fear of pain by getting help from a psychologist and trying relaxation or meditation techniques."

In the study, researchers evaluated 16 patients with chronic back pain and a control group of 18 healthy subjects.

The goal was to analyze the relationships between four factors: 1) cortisol levels, which were determined with saliva samples; 2) the assessment of clinical pain reported by patients prior to their brain scan (self-perception of pain); 3) hippocampal volumes measured with anatomical magnetic resonance imaging (MRI); and 4) brain activations assessed with functional MRI (fMRI) following hot/cold pain stimulations.

Data analysis also revealed that patients with a smaller hippocampus have higher cortisol levels and stronger responses to acute pain in a brain region involved in anticipatory anxiety in relation to pain.

The response of the brain to the painful procedure during the scan partly reflected the intensity of the patient's current clinical pain condition.

These findings support the chronic pain vulnerability model in which people with a smaller hippocampus develop a stronger stress response, which in turn increases their pain and perhaps their risk of suffering from chronic pain.

It is a nightmare situation. A person diagnosed as being in a vegetative state has an operation without anaesthetic because they cannot feel pain. Except, maybe they can.

Alexandra Markl at the Schön clinic in Bad Aibling, Germany, and colleagues studied people with unresponsive wakefulness syndrome (UWS) – also known as vegetative state – and identified activity in brain areas involved in the emotional aspects of pain. People with UWS can make reflex movements but can't show subjective awareness.

There are two distinct neural networks that work together to create the sensation of pain. The more basic of the two – the sensory-discriminative network – identifies the presence of an unpleasant stimulus. It is the affective network that attaches emotions and subjective feelings to the experience. Crucially, without the activity of the emotional network, your brain detects pain but won't interpret it as unpleasant.

Her team gave moderately painful electric shocks to 30 people with UWS, while scanning their brains using fMRI. Sixteen people had some kind of brain activation – seven only in the sensory network but nine in the affective network as well.

These results question whether some diagnoses should change from UWS to minimally conscious, which is characterised by some level of awareness.

"I don't think this paper alone will change the clinical approach to people with diagnoses such as UWS," says Donald Weaver at Dalhousie University in Halifax, Nova Scotia, Canada, who was not involved in the work. But it will encourage future study, he says.

Changing a diagnosis depends on whether neurologists are ready to accept alternative ways of diagnosing disorders of consciousness, says Boris Kotchoubey at the Institute of Medical Psychology and Behavioural Neurobiology in Tübingen, Germany, who worked on the study.

Nonetheless, Kotchoubey is confident that the way people with UWS are cared for will change, even if their diagnoses remain the same. "I know that many doctors working with such patients have been instructed to treat their patients as if they can understand them and perceive at least something in the environment, perhaps pain, pleasure, or emotion," he says.

But not all people are treated this way. Prior to the study, one of the people in Markl's study was given no anaesthesia before a tracheotomy, which involves an incision in the neck to allow breathing without using the nose or mouth. As people with UWS are clinically considered unable to understand pain, doctors do not have to give an anaesthetic.

When something causes less pain than expected it is even possible for it to feel pleasant, a new study reveals. These findings may one day play a key role in treating pain and substance abuse.

If you accidently kick your toe against a doorframe you are probably going to find it very painful. As a purely intellectual experiment, imagine purposefully kicking a doorframe hard enough to potentially break your toe. When it turns out your toe has been battered but not broken, the pain may be interpreted more as a relief.

"It is not hard to understand that pain can be interpreted as less severe when an individual is aware that it could have been much more painful. Less expected, however, is the discovery that pain may be experienced as pleasant if something worse has been avoided," explains Siri Leknes, Research Fellow at the Department of Psychology at the University of Oslo.

The lesser of two evils

When working as a research fellow at Oxford University, Dr Leknes became curious about what can be called the "it could have been worse" phenomenon. How is the experience of pain affected by a feeling of relief from realising that it was not as bad as expected?

Dr Leknes recruited 16 healthy subjects who prepared themselves for a painful experience. They were repeatedly exposed to heat of varying intensity applied to their arm for four seconds.

The experiments were carried out in two different contexts: in the first, the heat was either not painful or only moderately painful — about the same as firmly holding a coffee cup that is slightly too hot. In the second, the heat was either moderately or intensely painful. In this context, moderate pain was the lesser of two evils.

The research subjects reported how they interpreted the pain. In addition, while they were exposed to the stimuli their brain activity was measured by MRI.

What intrigued the researchers was the subjects' response to moderate pain. In the experiments where moderate pain was the worst alternative, the pain felt was unpleasant. In the instances where it was the best alternative, the subjects experienced the moderate pain as positive — even comforting.

"The likely explanation is that the subjects were prepared for the worst and thus felt relieved when they realised the pain was not going to be as bad as they had feared," states Dr Leknes.

"In other words, a sense of relief can be powerful enough to turn such an obviously negative experience as pain into a sensation that is comforting or even enjoyable."

The MRI examinations revealed that the brain changed how it processed moderate pain according to the context and what the alternative was. When the pain was comforting, there was more activity in the areas of the brain associated with pleasure and pain relief and less activity in the areas associated with pain.

A future in treating pain?

Dr Leknes believes that the study illustrates that exposure to one and the same stimulus is interpreted very differently among individuals and that the experience is connected to expectation and context. Some individuals like the burning sensation of eating chili peppers, for example, while others enjoy sadomasochistic sex.

Also, envisioning that an even worse alternative exists than what is actually experienced may even help a person to interpret involuntary pain as something agreeable.

Nevertheless, Dr Leknes points out, pain is generally a highly unpleasant experience and current pain alleviation treatments are inadequate for many people.

"That is why it is so important to find out how and to what degree the brain can control pain on its own. We are currently carrying out basic research, but we hope that this knowledge will one day be applied to develop improved methods for treating pain," she says.

Would it always be advisable then for a doctor to inform a patient that a procedure or treatment is going to be very painful?

"In some situations this may be a good approach, but not always," replies Dr Leknes. "Doctors observe that their patients react very differently to the information they are given; certain patients are likely to experience a genuine sense of relief if they prepare for the worst only to find it not so bad after all, whereas others prefer to avoid worrying beforehand and want to know as little as possible about what they will be undergoing," she explains.

Substance abuse — from pleasure to relief

The study has been partially funded under the Programme on Alcohol and Drug Research (RUSMIDDEL) at the Research Council of Norway. "Relief is also likely a vital factor in substance abuse," asserts Dr Leknes.

"Over time, the effect of alcohol and drugs will change from triggering feelings of pleasure to primarily alleviating the discomfort of addiction. The brain's regulatory processes change, causing substance abusers to experience a shift; at some point, they use alcohol and drugs in order to achieve a neutral state and avoid feeling awful," explains Dr Leknes.

"By studying relief in order to understand how this process works, we can come up with new ideas for treating substance dependence more effectively. From our pain research, we know that the relief mechanisms in the brains of patients with chronic pain become disrupted. This may be something shared by patients suffering from pain and alcohol and drug addiction alike," she concludes.

Among fibromyalgia patients taking either of two commonly prescribed drugs to reduce pain, 22 percent report substantial improvement while 21 percent had to quit the regimen due to unpleasant side effects, according to a new review in The Cochrane Library.

People with fibromyalgia suffer from chronic widespread pain, sleep problems and fatigue. The illness affects more than 5 million Americans, 80 percent of whom are women. The cause of fibromyalgia is unknown and currently there is no cure. Using a Quality of Life (QOL) scale for fibromyalgia, the studies reviewed reported QOL ratings lower than 15 on a scale of 0 to 100 even among patients on medications. The two medications often prescribed to treat fibromalgia are duloxetine, known by the brand name Cymbalta or milnacipran, commonly known as Savella.

"A frank discussion between the physician and patient about the potential benefits and harms of both drugs should occur," noted the reviewers, led by Winfried Häuser, M.D. of Technische Universität München.

The authors reviewed 10 high-quality studies comprising more than 6,000 adults who received either duloxetine, milnacipran, or a placebo for up to six months. A substantial majority of study participants were middle-aged, white women.

"This is a very important study," says Fred Wolfe, M.D. of the National Data Bank for Rheumatic Diseases. "There's an enormous amount of advertising suggesting that these drugs really help, whereas the research data show that the improvement is really minimal."

Treatment with drugs alone "should be discouraged," the reviewers added. Instead, the review authors recommend a multi-faceted treatment approach including medications for those who find them helpful, exercises to improve mobility and psychological counseling to improve coping skills.

"The medical field does poorly with the treatment of fibromyalgia in general," says Brian Walitt, M.D., M.P.H., a co-author of the review and an expert in pain syndromes at Washington Hospital Center in Washington, D.C. "Chasing [a cure] with medicine doesn't seem to work.The people who seem to me to do best sort of figure it out on their own by thinking about things, getting to know themselves, and making changes in their lives to accommodate who they've become," concludes Walitt.

The only other medication approved for fibromyalgia treatment in the U.S. is the anti-convulsant pregabalin, known by the brand name Lyrica. The Cochrane Library plans to publish a review of its effectiveness later this year.

Intensive neuroscientific research is needed to reveal the underlying causes of fibromyalgia and other pain syndromes, say the researchers. In the meantime, combinations of various medications as well as combinations of drug and non-drug treatments may offer better symptom control for sufferers.

Monday, February 25, 2013

We think of pain as a symptom, but there are cases where the nervous system develops feedback loops and pain becomes a terrifying disease in itself. Starting with the story of a girl whose sprained wrist turned into a nightmare, Elliot Krane talks about the complex mystery of chronic pain, and reviews the facts we're just learning about how it works and how to treat it.

Friday, February 22, 2013

Treating the brain with magnets went mainstream a few years ago, when the technique proved successful at relieving major depression. Now the procedure, repetitive transcranial magnetic stimulation (rTMS), shows promise for another mysterious, hard-to-treat disorder: chronic pain.

Until now, pain seemed out of reach for rTMS because the regions involved in pain perception lie very deep within the brain. The other disorders helped by rTMS all involve brain areas close to the skull. To treat depression, for example, a single magnetic coil directs a magnetic field at the dorsolateral prefrontal cortex, a region of the brain's outer folds. When aimed at different areas of these outer folds, rTMS improves the motor symptoms of Parkinson's disease, staves off the damage of stroke, lessens the discomfort that follows nerve injury and treats obsessive-compulsive disorder. The magnetic field affects the electrical signaling used by neurons to communicate, but how exactly it improves symptoms is unclear—scientists suspect rTMS may redirect the activity of select cells or even entire brain circuits.

To extend the technique's reach, David Yeomans, a neuroscientist at Stanford University, and his colleagues used four magnets rather than one and employed high-level math to steer the resulting complex fields. Their target was an area called the anterior cingulate cortex (ACC), an area active in the experience of all types of pain, regardless of its source or nature.

The researchers aimed the magnetic impulses at the ACC of healthy volunteers for 30 minutes. Immediately afterward, subjects underwent a PET scan of brain activity. During the scan, subjects reported minute-by-minute pain sensations from a hot plate applied to their arm. After rTMS, subjects rated their pain nearly 80 percent lower than they had before treatment, and the PET scan revealed blunted activity in the ACC.

Next the researchers tested the treatment on chronic pain in people with fibromyalgia, a mysterious pain syndrome that causes pain and tenderness all over the body. Patients received a daily dose from the magnets for four weeks and saw a reduction in their daily pain by almost half, which lasted for four weeks beyond treatment.

The study, presented at last October's meeting of the Society for Neuroscience in New Orleans, shows the potential of rTMS for many kinds of pain. The procedure has become increasingly common and available since 2008, when the Food and Drug Administration approved it for treating major depression. "More psychiatrists are bringing it into their armamentarium," Yeomans says. Now that it appears this noninvasive technique "can affect pain without putting new molecules into your body," he adds, relief may be close for people for whom drug therapies have failed or simply do not exist.

$300 - Cost of a typical transcranial magnetic stimulation (TMS) session. TMS therapies often include 20 to 30 sessions, at a total cost of between $6,000 and $10,000.

12/08 - Date the FDA approved TMS in the U.S. to treatmajor depression in adults who had failed to improve on an antidepressant regimen. Canada had granted the same approval six years earlier.

1 - Number of conditions TMS is approved to treat: major depressive disorder. Research suggests the technique can also help people with post-traumatic stressdisorder, bipolar disorder and Parkinson's disease, among other ailments.

387 - Number of recent clinical trials testing TMS for a variety of conditions, including schizophrenia, anorexia, Alzheimer's disease, autism and cerebral palsy.

1985 - Year TMS was first developed and tested. Anthony T. Barker of Royal Hallamshire Hospital in Sheffield, England, used the machine to noninvasively stimulate the cerebral cortex

Fibromyalgia should be considered a condition that exists across a continuum in the population, and is not a categorical disorder as it has often been considered, researchers concluded from a survey analysis in Germany.

On a polysymptomatic distress scale, patients with fibromyalgia had mean scores of 16.4 out of 27, compared with mean scores of 3 in the general German population, according to Frederick Wolfe, MD, of the National Data Bank for Rheumatic Diseases in Wichita, Kan., and colleagues.

With the cutoff diagnostic score being 12 on that scale, 2.1% of the population met the criteria for fibromyalgia, but continuous and linear correlations were seen throughout the population sample for multiple relevant disease domains including pain, physical and psychological distress, and quality of life (P<0.001 for all), the researchers reported online in Arthritis Care & Research.

"We found strong evidence that fibromyalgia is not a discrete -- yes or no -- disorder. Rather, the symptoms that characterize fibromyalgia exist in a continuum from none to very severe across all people in the population," lead author Wolfe told MedPage Today.

"In those with fibromyalgia there is overwhelming polysymptomatic distress, with severe pain and severe symptoms of all sorts," Wolfe explained.

"One doesn't either have fibromyalgia or not have it," he added.

The publication in 2010 of revised diagnostic criteria for fibromyalgia, eliminating the requirement for tender points and emphasizing the importance of a wide variety of symptoms, made population-based studies of the condition more feasible.

Accordingly, Wolfe and colleagues identified a representative sample of 2,445 German adults who completed questionnaires on health, diet, education, and sociodemographics.

"The most important finding of the study is the idea that fibromyalgia is more of a dimensional disorder than a disease," said Brian Walitt, MD, of Georgetown University in Washington, who was not involved in the study.

"That's a very big departure from how people like to think about fibromyalgia," Walitt told MedPage Today.

Fibromyalgia was assessed on the summary polysymptomatic distress scale, as well as on the scale's individual components of the widespread pain index and the symptom severity score as established in the 2010 criteria.

Those revised criteria required patients to have a score of 7 or higher on the widespread pain index and a symptom severity score of 5 or higher, or a pain index score between 3 and 6 and a symptom severity score of 9 or higher. Either variation led to polysymptomatic distress scores of 12 or higher.

The researchers found that the prevalence of fibromyalgia increased significantly with age, being 0.8% in adults younger than 40, rising to 2.5% for those between 40 and 60 and then to 3% for those older than 60 (P=0.004).

The summary polysymptomatic distress score rose by 0.59 units for each decade of life, while the symptom severity score increased by 0.14 units and the widespread pain index rose by 0.45 units.

The widespread belief that women are more commonly afflicted was not borne out, since the prevalence was similar in women and men, at 2.4% and 1.8%, respectively (P=0.372).

In clinical practice before the revised diagnostic criteria were implemented, up to 90% of patients with fibromyalgia have been women, which may have related to their greater likelihood for having tender points and possibly for seeking medical care for these concerns, the researchers observed.

The analysis also identified a strong correlation (r=0.790) between polysymptomatic distress scores and scores on a somatic symptom questionnaire that reflects how severely a person is distressed by symptoms such as fatigue, unrefreshing sleep, and gastric discomfort.

This was shown by the finding that for a diagnosis of fibromyalgia, the area under the receiver operating curve for the polysymptomatic distress score was 0.996 and was similar, at 0.973, for the somatic symptom score, according to the researchers.

Overall, 53.8% of individuals with fibromyalgia had one or more severe somatic symptoms, while 32.7% had two or more, and 38.5% would qualify as having a physical symptom disorder in the proposed DSM-V.

While the prevalence of fibromyalgia in Germany was only about 2%, estimates from the U.S. have been slightly higher, at about 4%.

It's unclear whether this reflects a difference in the populations or more refined measuring techniques, Walitt pointed out.

"Although fibromyalgia in clinical practice is treated as a categorical disorder, the confirmation of fibromyalgia as a spectrum disorder has important research, clinical, and societal connotations," the researchers wrote.

"Future research, whether clinical or neurobiological, must account for the continuum nature of fibromyalgia to be valid," they argued in conclusion.

Monday, February 18, 2013

Syracuse, N.Y. – Central New Yorkers with prescriptions for Vicodin and other painkillers containing hydrocodone will not be able to get them refilled starting Saturday unless they go to their doctor for a new prescription.

The change is required by the state's new I STOP law, designed to address the epidemic of prescription painkiller abuse and addiction sweeping Central New York and the rest of the nation.

Hydrocodone will become classified as a schedule 2 drug Saturday. That means refills will no longer be allowed for hydrocodone prescriptions. Even people holding hydrocodone prescriptions authorized for more refills won't be able to refill them starting Saturday.

"What we've been doing is warning our patients that they will need a new prescription the next time," said Selig Corman of the Pharmacists Society of the State of New York.

Hydrocodone is a type of drug known as an "opioid." Opiods can create intense feelings of euphoria or well-being. They are synthetic versions of opiate drugs such as morphine and heroin, derived from the opium poppy. Hydrocodone is usually combined with other drugs such as acetaminophen. Some of the popular brand-name prescription drugs containing hydrocodone include Vicodin, Lortab and Tussionex.

Dr. Brian Johnson, director of addiction medicine at Upstate, said patients are often prescribed enough hydrocodone after surgery to last them several months, when they should only get enough for a few days.

The number of prescriptions written in Central New York for the two most popular prescription painkillers — hydrocodone and oxycodone — soared between 2007 and 2011, according to the state Health Department. Hydrocodone prescriptions increased more than 50 percent, from 181,993 in 2007 to 274,293 in 2011, while oxycodone prescriptions jumped by nearly 90 percent, from 64,755 in 2007 to 122,415 in 2011.

Also starting Saturday, Tramadol, a prescription muscle relaxant drug, will become classified as a schedule 4 drug as part of the I STOP law. Brand name versions of the drug include Ultram, Ultacet and Ryzolt. There are no limits on how much Tramadol can be prescribed now. Under the new classification, doctors will only be allowed to prescribe a 30-day supply of Tramadol with five refills. People with prescriptions for Tramadol issued before Saturday can get them refilled as long as the prescription is not more than 6 months old and the number of authorized refills does not exceed five.

Johnson of Upstate is happy about the changes. "It has to do with raising consciousness of how addictive these drugs are," he said.

Patients are often incorrectly told Tramadol is not addictive, then they end up in detox programs, Johnson said.

The new restrictions may create problems for some chronic pain patients and their doctors, said Dr. Joseph Catania of the New York Spine and Wellness Center, a pain management practice with offices in North Syracuse and DeWitt.

Catania said he agrees with the law's intent to curb diversion and abuse of painkillers. "But this prevents a medical office from using some judgment to determine the required follow up visit," he said.

Patients who are stable and only need to see their doctor every several months now will have to schedule office visits monthly, he said.

"This is going to create a flood of patients into the medical community who may not have that type of routine access to care," he said. "It will impact all of us in how we take care of patients."

Under the new regulation, doctors can prescribe 90-day supplies of hydrocodone for chronic pain patients.

The prescribing changes are just the first of several provisions in the I STOP law designed to overhaul the way prescription drugs are distributed and tracked in New York. The law will require doctors beginning Aug. 27 to consult an electronic prescription database when they are prescribing controlled substances. The database, being developed by the state, will include information about controlled substances – drugs regulated by federal law -- dispensed by pharmacies on a real time basis. The intent of the database is to prevent "doctor shoppers" from obtaining prescriptions from multiple physicians.

The law also will eventually mandate that all controlled substances be prescribed electronically.

Mindfulness meditation training in awareness of present moment experience, such as body and breath sensations, prevents depression and reduces distress in chronic pain. In a new paper, Brown University scientists propose a neurophysiological framework to explain these clinical benefits.

A matter of sensory cortical alpha rhythms

Repeated local sensory focus -- on a hand, say -- develops control over underlying neurophysiological mechanisms that may help manage chronic pain or other problems.Why does training in mindfulness meditation help patients manage chronic pain and depression? In a newly published neurophysiological review, Brown University scientists propose that mindfulness practitioners gain enhanced control over sensory cortical alpha rhythms that help regulate how the brain processes and filters sensations, including pain, and memories such as depressive cognitions.

The proposal, based on published experimental results and a validated computer simulation of neural networks, derives its mechanistic framework from the intimate connection in mindfulness between mind and body, since standardized mindfulness meditation training begins with a highly localized focus on body and breath sensations. This repeated localized sensory focus, the scientists write, enhances control over localized alpha rhythms in the primary somatosensory cortex where sensations from different body are "mapped" by the brain.

In effect, what the researchers propose in their paper in Frontiers in Human Neuroscience, is that by learning to control their focus on the present somatic moment, mindfulness meditators develop a more sensitive "volume knob" for controlling spatially specific, localized sensory cortical alpha rhythms. Efficient modulation of cortical alpha rhythms in turn enables optimal filtering of sensory information. Meditators learn not only to control what specific body sensations they pay attention to, but also how to regulate attention so that it does not become biased toward negative physical sensations such as chronic pain. The localized attentional control of somatosensory alpha rhythms becomes generalized to better regulate bias toward internally focused negative thoughts, as in depression.

"We think we're the first group to propose an underlying neurophysiological mechanism that directly links the actual practice of mindful awareness of breath and body sensations to the kinds of cognitive and emotional benefits that mindfulness confers," said lead author Catherine Kerr, assistant professor (research) of family medicine at the Alpert Medical School and director of translational neuroscience for the Contemplative Studies Initiative at Brown.

Experimental evidence

In experiments that Kerr and neuroscientist co-authors Stephanie Jones and Christopher Moore have published over the last few years, the team has used a brain imaging technology called magnetoencephalography (MEG) to show that alpha rhythms in the cortex correlate with sensory attention and that the ability to regulate localized alpha brainwaves on a millisecond scale is more distinct in people who have had standardized mindfulness training than in those who have not. The trio led these experiments at the Massachusetts Institute of Technology, Harvard, and Massachusettes General Hospital before they all came to Brown in 2011.

In one experiment published in the Journal of Neuroscience in 2010, they observed that when people focused their attention on sensations in the left hand, the corresponding "map" for the hand in the cortex showed a marked drop in alpha wave amplitude (as if to reduce filtering there). When the subjects' attention shifted away from that body part, the alpha rhythm amplitude in the corresponding brain map went back up (as if restoring the alpha filter). Other research groups have shown this to be the case for other kinds of attention-related tasks including focusing spatial attention and working memory.

Then in 2011 in Brain Research Bulletin, the team published another paper. They randomized subjects to eight weeks of mindfulness training versus a control group. In MEG, they asked members of each group to focus attention on sensations in their hand and then to switch their attention to their foot. The people trained in mindfulness displayed quicker and larger changes in alpha wave amplitude in their brain's hand map when they made the attentional shift than the six people who did not have mindfulness training.

Mindful computational model

In addition to the emerging experimental evidence, the research framework is also informed by a computer model that Jones has developed to simulate the alpha brainwaves through reciprocal interactions between the cortex, which processes information and thoughts, and the thalamus, which is like a switchboard that mediates information flow from the rest of the brain to the cortex. The model is well validated in that it produces alpha rhythms that closely match those observed in live MEG scans of real subjects.

Jones, assistant professor (research) of neuroscience, did not originally develop the model to aid meditation research.

"We were investigating what are the brain mechanisms that can create this prominent alpha rhythm and mediate its impact on sensory processing," Jones said. "The model simulates the electrical activity of neural networks and makes very specific predictions about how this rhythm is generated. Once we understand the brain processes regulating alpha rhythm expression, we can better understand how it can be modulated with mindfulness practice and why this is beneficial."

Among the most important predictions is one that could explain how gaining control of alpha rhythms not only enhances sensory focus on a particular area of the body, but also helps people overcome persistent competing stimuli, such as depressive thoughts or chronic pain signals.

To accomplish this, the model predicts, meditators must achieve proper control over the relative timing and strength of alpha rhythms generated from two separate regions of the thalamus, called thalamic nuclei, that talk to different parts of the cortex. One alpha generator would govern the local "tuning in," for instance of sensations in a hand, while the other would govern the broader "tuning out" of other sensory or cognitive information in the cortex.

It's a bit like focusing a telescope by precisely aligning the position of two different lenses. The authors' framework hypothesizes that experienced meditators gain the ability to turn that proverbial focus knob to align those different rhythms.

Working with the framework

In the new paper the authors propose that training chronic pain patients in the standardized mindfulness techniques of focusing on and then focusing away from pain, should result in MEG-measurable, testable improvements in alpha rhythm control.

"By this process of repeatedly engaging and disengaging alpha dynamics across the body map, according to our alpha theory, subjects are re-learning the process of directly modulating localized alpha rhythms," they wrote. "We hypothesize that chronic pain patients trained in mindfulness will show increased ability to modulate alpha in an anticipatory tactile attention paradigm similar to that used in [the 2011 study]."

Many such experiments are yet to be done, Kerr acknowledges, and her group can only do so many.

"There are a number of hypotheses in this framework that can be tested," Kerr said. "That's one of the reasons we wanted to put this out as a framework. It is beyond our ability to test all of these ideas. We wanted to make this available to the scientific field and present this unified view."

In addition to Kerr, Jones, and Moore, the paper's other authors are Matthew Sacchet of Stanford University and Sara Lazar of Massachusetts General Hospital.

The team's research has received support from the National Institutes of Health, the Hershey Family Foundation, and the Osher Institute.

Wednesday, February 06, 2013

Noxious stimuli often evoke very different pain experience across subjects, as documented both by verbal report and by the observation of pain behaviour. Moreover, the same stimulus or disease condition typically yields very different pain experience in the same individual over time. "Nonspecific" conditions such as distraction, stress, anticipation and placebo, for example, can radically alter pain experience.

Major advances have been made in recent years in the understanding of how brain mechanisms modulate pain experience. Generalities such as "it's psychological" have given way to the discovery of specific modulating brain circuits (e.g., descending inhibition from midbrain PAG) and mediators (e.g., amino acid neurotransmitters and their variety of modifiable receptors, endogenous opioids and cannabinoids, cytokines). Individual differences once referred to "high pain threshold" are being understood as due to genetic polymorphisms, changes in gene transcription or epigenetic regulation of neuronal networks. These insights open entirely new frontiers to advanced students and future young investigators. For example, while a few instances of pain suppression are known to be opioidergic, many are mediated by other, still unknown mechanisms. Discoveries that can be anticipated could change the face of pain therapeutics.

The European Pain School 2013 will explore the domain of brain modulation of individual pain experience. Disciplines that will be brought to bear on the problem range from psychology to molecular genetics, with a predictable cross-fertilization of ideas. Modulation subsumes multiple mechanisms that have become known by experimental research on animal and human subjects, as well as by clinical medical and psychological research on patients.

Contemporary pain science has attained high standards and is acknowledged as an academic discipline worldwide. Likewise, pain medicine is currently emerging as a medical subject with a great integrative potential against the centrifugal and often fragmented tendencies of much of contemporary practical medicine. The International Association for the Study of Pain (IASP) and its worldwide chapters provide impetus to this process, resulting in the advancement of interdisciplinary programs for the ultimate benefit of pain patients. The European Pain School is focused on advancing this new vision among junior investigators interested in basic and clinical research.